Growth Hormone, Acromegaly, and Heart Failure: An Intricate Triangulation

Luigi Saccà, Raffaele Napoli, Antonio Cittadini

Disclosures

Clin Endocrinol. 2003;59(6) 

In This Article

Impact of GH on Ventricular Geometry and Forces

The consequences of relatively short-term GH excess on cardiac morphology and function are quite straightforward, and differ substantially from the pattern observed in advanced acromegaly. Cardiac growth is prominent in both conditions and causes marked thickening of the ventricular wall. However, in long-term acromegaly there is often cavity dilation, which is particularly pronounced in the presence of decompensated cardiomyopathy. In contrast, in short-term acromegaly the marked thickening of the ventricular wall is not accompanied by cavity dilation, so that the relative wall thickness (LV wall thickness/LV radius) is increased (Fazio et al., 2000). This geometric pattern, for reasons inherent in the law of Laplace (wall stress = LV pressure/LV relative wall thickness), causes a decrease in the ventricular load (wall stress) and, consequently, enhances the LV pump activity. Indeed, in patients with short-term acromegaly cardiac output is augmented (Thuesen et al., 1988; Fazio et al., 2000), whereas afterload and peripheral vascular resistance are decreased (hyperkinetic status).

In animal models (Cittadini et al., 1996, 1997), GH increased LV mass and wall thickness. GH also increased the size and cross-sectional area of cardiomyocytes in the failing myocardium (Grimm et al., 1998; Houck et al., 1999), suggesting that, in essence, the growth effect of GH is to induce parallel apposition of new sarcomeres. In moststudies (Castagnino et al., 1992; Yang et al., 1995; Cittadini et al., 1997; Grimm et al., 1998; Houck et al., 1999; Tajima et al., 1999; King et al., 2001), but not in all (Shen et al., 1996, 1998), the growth effect of GH and IGF-I on the failing heart was accompanied by functional benefit.

The increased LV mass and wall thickness observed in short-term acromegaly has no negative impact on diastolic function. The indices of ventricular relaxation and filling remain within the normalrange (Fazio et al., 2000). This pattern is very similar to that observed after acute administration of GH to normal subjects for 4 weeks. In this model, the LV relative wall thickness increases, wall stress falls, and diastolic function remains unmodified (Cittadini et al., 2002). In addition, LV performance is enhanced by acute GH administration (Cittadini et al., 2002).

Both GH and heart failure act as potent growth stimuli and cause marked increase in LV mass. However, GH reshapes the heart according to a concentric pattern of hypertrophy, with consequent ventricular unloading and functional benefit. In contrast, in heart failure the growth energy is dissipated towards progressive enlargement of the ventricular cavity (eccentric remodelling), while wall thickness remains inappropriately small. Ultimately, in heart failure, as well as in advanced acromegaly, the relative wall thickness is reduced, while wall stress rises critically and impacts negatively on ventricular mechanics ( Table 2 ).

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